Abstract: "The development of a radiosensitivity predictive assay is an attractive goal in radiation Oncology. Since there is a high degree of inter-patient variability in the inherent sensitivity or resistance to therapy, it is crucial to have the ability to identify molecular markers that correlate with sensitivity or resistance to radiation treatment. We have applied Raman micro-spectroscopy (RMS) in vitro to discriminate between the ovarian carcinoma cell lines A2780s (parental wild type) and A2780cp (cisplatin cross radio-resistant variant). These two cell lines represent a good model of tumor tissues of similar origin but with different intrinsic chemo- and radio-sensitivities. Moreover, their radiobiological behavior has been extensively studied and their survival curves under different irradiation schemes are known. The Raman spectra collected from individual cells undergo initial preprocessing (background subtraction, normalization and noise reduction) to yield true Raman spectra representative of the cells. The mean of these spectra are analyzed with Principal Component Analysis (PCA) followed by Linear Discriminant Analysis (LDA) to yield a strong separation between the cell lines. The objective of this ongoing work is to characterize the spectral differences between the two cell types in order to determine the underlying biochemical basis for this separation. The multivariate classification model constructed using such Raman spectra of ovarian cancer cells could potentially be utilized for early prediction of tumor response."

2. Talk on 2016 paper by Richard Richardson and Mary-Ellen Harper, University of Ottawa: "Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy"

By Richard Richardson, Canadian Nuclear Laboratories, Chalk River

Abstract: It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may explain difficulty in eliminating hypoxic tumor cells, a major cause of regrowth after therapy. Our analysis utilizes the Howard-Flanders and Alper formula, which describes the relationship of radiosensitivity with oxygen tension. Here, we assign and qualitatively assess the relative contributions of two important mechanisms. The first mechanism involves the emission of reactive oxygen species from the mitochondrial electron transport chain, which increases with oxygen tension. The second mechanism is related to an energy and repair deficit, which increases with hypoxia. Following a radiation exposure, the uncoupling of the oxidative phosphorylation system (proton leak) in mitochondria lowers the emission of reactive oxygen species which has implications for fractionated radiotherapy, particularly of hypoxic tumors. Our analysis shows that, in oxygenated tumor and normal cells, mitochondria, rather than the nucleus, are the primary loci of radiotherapy effects, especially for low linear energy transfer radiation. Therefore, the oxygen effect can be explained by radiation-induced effects in mitochondria that generate reactive oxygen species, which in turn indirectly target nuclear DNA.